Systematic variation in gene expression patterns in human cancer cell lines

We used cDNA microarrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumours from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumours in vivo.     

Trifluoroacetyl as a protecting group for amino acid hydrazides

Zusammenfassung Die Bildung von Z-N²-Trifluoroacetyl-Aminosäure-Hydraziden wird beschrieben. Die Anwendungsmöglichkeiten dieser Verbindungen in der Peptidsynthese werden durch mehrere Beispiele demonstriert.     

Reputed rat scotophobin prepared by a solid-phase procedure shown invalid by comparison with a product derived from a classical synthesis on the basis of physical and biological properties

Zusammenfassung Eine Synthese von Scotophobin mit klassischen Methoden ergab ein Produkt, das sich vom natürlichen Peptid hinsichtlich seiner biologischen, chromatographischen und physiologischen Eigenschaften unterschied. Es wird daraus gefolgert, dass die für das natürliche Produkt vorgeschlagene Strukturformel nicht korrekt ist.     

Synthesis of a structure proposed for scotophobin

Zusammenfassung Es wurde ein biologisch interessantes Polypeptid mit der für Scotophobin vorgeschlagenen Sequenz synthetisiert. Da dieses nur eine geringe biologische Aktivität besass, wird angenommen, dass die für das natürliche Produkt vorgeschlagene Strukturformel nicht korrekt ist.

---

---

We thank the National Institutes of Health (MH 19320) for the support of this work.     

Endothelial tubes assemble from intracellular vacuoles in vivo

The formation of epithelial tubes is crucial for the proper development of many different tissues and organs, and occurs by means of a variety of different mechanisms. Morphogenesis of seamless, properly patterned endothelial tubes is essential for the development of a functional vertebrate circulatory system, but the mechanism of vascular lumenization in vivo remains unclear. Evidence dating back more than 100 years has hinted at an important function for endothelial vacuoles in lumen formation. More than 25 years ago, in some of the first endothelial cell culture experiments in vitro, Folkman and Haudenschild described "longitudinal vacuoles" that "appeared to be extruded and connected from one cell to the next", observations confirmed and extended by later studies in vitro showing that intracellular vacuoles arise from integrin-dependent and cdc42/Rac1-dependent pinocytic events downstream of integrin-extracellular-matrix signalling interactions. Despite compelling data supporting a model for the assembly of endothelial tubes in vitro through the formation and fusion of vacuoles, conclusive evidence in vivo has been lacking, primarily because of difficulties associated with imaging the dynamics of subcellular endothelial vacuoles deep within living animals. Here we use high-resolution time-lapse two-photon imaging of transgenic zebrafish to examine how endothelial tubes assemble in vivo, comparing our results with time-lapse imaging of human endothelial-cell tube formation in three-dimensional collagen matrices in vitro. Our results provide strong support for a model in which the formation and intracellular and intercellular fusion of endothelial vacuoles drives vascular lumen formation.     

Coincidence and reproducibility in the EHT black hole experiment

This paper discusses some philosophical aspects related to the recent publication of the experimental results of the 2017 black hole experiment, namely the first image of the supermassive black hole at the center of galaxy M87. In this paper I present a philosophical analysis of the 2017 Event Horizon Telescope (EHT) black hole experiment. I first present Hacking's philosophy of experimentation. Hacking gives his taxonomy of elements of laboratory science and distinguishes a list of elements. I show that the EHT experiment conforms to major elements from Hacking's list. I then describe with the help of Galison's Philosophy of the Shadow how the EHT Collaboration created the famous black hole image. Galison outlines three stages for the reconstruction of the black hole image: Socio-Epistemology, Mechanical Objectivity, after which there is an additional Socio-Epistemology stage. I subsequently present my own interpretation of the reconstruction of the black hole image and I discuss model fitting to data. I suggest that the main method used by the EHT Collaboration to assure trust in the results of the EHT experiment is what philosophers call the Argument from Coincidence. I show that using this method for the above purpose is problematic. I present two versions of the Argument from Coincidence: Hacking's Coincidence and Cartwright's Reproducibility by which I analyse the EHT experiment. The same estimation of the mass of the black hole is reproduced in four different procedures. The EHT Collaboration concludes: the value we have converged upon is robust. I analyse the mass measurements of the black hole with the help of Cartwright's notion of robustness. I show that the EHT Collaboration construe Coincidence/Reproducibility as Technological Agnosticism and I contrast this interpretation with van Fraassen's scientific agnosticism.     

Failure of wild-type or a mutant form of protein kinase C-alpha to transform fibroblasts

A mutant form of the alpha-isoform of protein kinase C (PKC) was recently isolated from an ultraviolet radiation-induced murine fibrosarcoma cell line and reported to transform mouse BALB/c 3T3 fibroblasts on transfection. Four point mutations in the regulatory domain were assumed to be responsible for its oncogenicity and unusual preference for membrane localization. Here, we report that overexpression of the reported mutant PKC alpha complementary DNA in three fibroblast cell lines, including BALB/c 3T3, does not enable these cells to grow in soft agar or nude mice. In addition, this mutant PKC alpha form seems to be indistinguishable from the wild-type PKC alpha with respect to its dependence on cofactors, phorbol ester binding, subcellular distribution and its effects on growth and morphology. These results fail to confirm the previous study and indicate that overexpression of either the wild-type or the reported mutant form of PKC alpha does not transform rodent fibroblasts.